(1) Limited evidence suggests that cPLA2, which selectively releases arachidonic acid from membrane phospholipids, and COX-2, the rate limiting enzyme for prostanoid synthesis, may be affected by aging. We examined the expression of these two enzymes in the hippocampus, frontal pole and cerebellum from young adult (2-5 years old), middle-aged (8-11 years old) and aged (23 years old) Rhesus monkeys. Although the enzyme activity of both cPLA2 or COX was not significantly changed in the different age groups, the cPLA2 protein level was decreased in the cerebellum from middle-aged and aged monkeys compared to young adults, whereas COX-2 protein level was decreased in the frontal pole from middle-aged and aged monkeys compared to young adults. These results suggest that the decrease in protein levels of the two enzymes might be caused by age-related cell loss, and that the reported up-regulation in cPLA2 and COX-2 expression observed in Alzheimer?s disease is specifically related to disease pathology and not to physiological aging.